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To obtain the same pain relief the dose must be increased. If these drugs are taken for long periods, very large doses might be needed to provide adequate pain control. These required doses can become so large that if they were taken before the tolerance had developed, death could well have been the result.

It is this development of tolerance, and its rapid loss once the drugs stop, that often leads to the accidental death of people who self-administer opiates, especially heroin. If there is a break in supply and the acquired tolerance is lost, a sudden resumption may result in an unexpected fatal overdose.